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Updated: Jun 12, 2025

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Rare Genetic Variants of NLRP12 in Admixed Latino-American Children With SARS-CoV-2-Related Multisystem Inflammatory
Thaís M M Barreto1,2, Roberta S Souza3, Raquel B São Pedro1
1Instituto de Biologia, Universidade Federal da Bahia, Salvador.
Abstract:
Multisystem inflammatory syndrome in children (MIS-C) is a rare, potentially fatal complication of SARS-CoV-2 infection. Genetic defects in inflammation-related pathways have been linked to MIS-C, but additional research is needed, especially in diverse ethnic groups. The present study aimed to identify genetic variants underlying MIS-C in Brazilian patients. Whole exome sequencing was performed, focusing on genes involved in the host immune response to SARS-CoV-2. Functional assays assessed the impact of selected variants on nuclear factor-κB signaling. Nine rare, potentially deleterious variants were found in 8 of 21 patients, located in the IL17RC, IFNA10, or NLRP12 gene. Unlike the wild type NLRP12 protein, which inhibits nuclear factor-κB activation in HEK 293T cells, the mutant NLRP12 proteins have significantly reduced inhibitory properties. In conclusion, our results indicate that rare autosomal variants in immune-related genes may underlie MIS-C, highlighting the potential role of NLRP12 in its predisposition. These findings provide new insights for the appropriate management of MIS-C.
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